Using Polymers as Crystal Inhibitors to Prevent the Crystallization of the Rotigotine Patch.

Abstract

This study aimed to enhance the stability of the Rotigotine (ROT) patch using polymers as crystal inhibitors. Three polymers (Poloxamer 188, Soluplus, TPGS) were selected as crystal inhibitors to formulate ROT patches with varying drug loadings (20%, 40%, 60%, and 80%, w/w). SEM and XRD analysis revealed that the Soluplus and Soluplus-TPGS groups with a high concentration (80%, w/w) of ROT could be stored at room temperature for at least 90 days without crystallization. Moreover, the crystallization nucleation time and growth rate were utilized to assess the ability of Poloxamer 188, Soluplus, and TPGS to hinder the formation of ROT crystals and slow down its crystallization rate. Molecular docking results elucidated the intermolecular forces between ROT and different polymers, revealing their mechanisms for crystal inhibition. The ROT-Soluplus-TPGS combination exhibited the lowest binding free energy (-5.3 kcal/mol), indicating the highest binding stability, thereby effectively reducing crystal precipitation. In vitro skin permeation studies demonstrated that ROT patches containing crystal inhibitors exhibited promising transdermal effects. With increasing ROT concentration, the cumulative drug permeation substantially increased, while the lag time was notably reduced. This study offers novel insights for the development of ROT patches.